UniProtKB - Q9BXY4 (RSPO3_HUMAN)
R-spondin-3
RSPO3
Functioni
Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (PubMed:21727895, PubMed:21909076, PubMed:22615920).
Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity) (PubMed:21727895, PubMed:21909076, PubMed:22615920).
Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 (PubMed:29769720).
By similarity4 PublicationsGO - Molecular functioni
- frizzled binding Source: Ensembl
- heparin binding Source: UniProtKB-KW
- signaling receptor binding Source: UniProtKB
GO - Biological processi
- blood vessel remodeling Source: UniProtKB
- branching involved in labyrinthine layer morphogenesis Source: Ensembl
- positive regulation of canonical Wnt signaling pathway Source: Ensembl
- positive regulation of non-canonical Wnt signaling pathway Source: UniProtKB
- positive regulation of Wnt signaling pathway Source: UniProtKB
- positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: ParkinsonsUK-UCL
- sprouting angiogenesis Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Heparin-binding |
Biological process | Sensory transduction, Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9BXY4 |
Reactomei | R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-8939256, RUNX1 regulates transcription of genes involved in WNT signaling |
SignaLinki | Q9BXY4 |
SIGNORi | Q9BXY4 |
Names & Taxonomyi
Protein namesi | Recommended name: R-spondin-3Alternative name(s): Protein with TSP type-1 repeat Short name: hPWTSR Roof plate-specific spondin-3 Short name: hRspo3 Thrombospondin type-1 domain-containing protein 2 |
Gene namesi | Name:RSPO3 Synonyms:PWTSR, THSD2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20866, RSPO3 |
MIMi | 610574, gene |
neXtProti | NX_Q9BXY4 |
VEuPathDBi | HostDB:ENSG00000146374 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular region Source: Reactome
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 106 | F → A: Loss of LGR4/5/6-binding, no effect on WNT3A signaling; when associated with A-110. 1 Publication | 1 | |
Mutagenesisi | 110 | F → A: Loss of LGR4/5/6-binding, no effect on WNT3A signaling; when associated with A-106. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 84870 |
OpenTargetsi | ENSG00000146374 |
PharmGKBi | PA134885289 |
Miscellaneous databases
Pharosi | Q9BXY4, Tbio |
Genetic variation databases
BioMutai | RSPO3 |
DMDMi | 74752442 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
ChainiPRO_0000234443 | 22 – 272 | R-spondin-3Add BLAST | 251 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 36 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 41 ↔ 48 | PROSITE-ProRule annotation | ||
Disulfide bondi | 45 ↔ 54 | PROSITE-ProRule annotation | ||
Disulfide bondi | 57 ↔ 76 | PROSITE-ProRule annotation | ||
Disulfide bondi | 80 ↔ 95 | PROSITE-ProRule annotation | ||
Disulfide bondi | 98 ↔ 105 | PROSITE-ProRule annotation | ||
Disulfide bondi | 102 ↔ 111 | PROSITE-ProRule annotation | ||
Disulfide bondi | 114 ↔ 125 | PROSITE-ProRule annotation | ||
Disulfide bondi | 129 ↔ 142 | PROSITE-ProRule annotation | ||
Disulfide bondi | 148 ↔ 190 | PROSITE-ProRule annotation | ||
Disulfide bondi | 159 ↔ 166 | PROSITE-ProRule annotation | ||
Disulfide bondi | 199 ↔ 206 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q9BXY4 |
MassIVEi | Q9BXY4 |
PaxDbi | Q9BXY4 |
PeptideAtlasi | Q9BXY4 |
PRIDEi | Q9BXY4 |
ProteomicsDBi | 79540 [Q9BXY4-1] 79541 [Q9BXY4-2] |
PTM databases
GlyGeni | Q9BXY4, 1 site |
iPTMneti | Q9BXY4 |
PhosphoSitePlusi | Q9BXY4 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000146374, Expressed in myometrium and 188 other tissues |
Genevisiblei | Q9BXY4, HS |
Organism-specific databases
HPAi | ENSG00000146374, Tissue enhanced (endometrium) |
Interactioni
Subunit structurei
Interacts with the extracellular domain of FZD8 and LRP6 (By similarity). It however does not form a ternary complex with FZD8 and LRP6 (By similarity).
Interacts with WNT1 (By similarity). Binds heparin.
Interacts with LGR4, LGR5 and LGR6 (PubMed:21727895, PubMed:21909076, PubMed:22615920).
By similarity3 PublicationsGO - Molecular functioni
- frizzled binding Source: Ensembl
- signaling receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 124315, 6 interactors |
CORUMi | Q9BXY4 |
IntActi | Q9BXY4, 5 interactors |
MINTi | Q9BXY4 |
STRINGi | 9606.ENSP00000349131 |
Miscellaneous databases
RNActi | Q9BXY4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 35 – 86 | FU 1Add BLAST | 52 | |
Repeati | 92 – 135 | FU 2Add BLAST | 44 | |
Domaini | 147 – 207 | TSP type-1PROSITE-ProRule annotationAdd BLAST | 61 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 201 – 272 | DisorderedSequence analysisAdd BLAST | 72 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 207 – 222 | Basic residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 223 – 263 | Basic and acidic residuesSequence analysisAdd BLAST | 41 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | KOG3525, Eukaryota |
GeneTreei | ENSGT00940000157815 |
HOGENOMi | CLU_064219_0_0_1 |
InParanoidi | Q9BXY4 |
OMAi | WFFITLN |
OrthoDBi | 1441603at2759 |
PhylomeDBi | Q9BXY4 |
TreeFami | TF331799 |
Family and domain databases
CDDi | cd00064, FU, 1 hit |
Gene3Di | 2.20.100.10, 1 hit |
InterProi | View protein in InterPro IPR006212, Furin_repeat IPR009030, Growth_fac_rcpt_cys_sf IPR042994, RSPO3 IPR043601, Rspo_Fu-CRD_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf IPR044004, TSP1_spondin_dom |
PANTHERi | PTHR46987:SF1, PTHR46987:SF1, 2 hits |
Pfami | View protein in Pfam PF15913, Furin-like_2, 1 hit PF19028, TSP1_spondin, 1 hit |
SMARTi | View protein in SMART SM00261, FU, 2 hits SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS50092, TSP1, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MHLRLISWLF IILNFMEYIG SQNASRGRRQ RRMHPNVSQG CQGGCATCSD
60 70 80 90 100
YNGCLSCKPR LFFALERIGM KQIGVCLSSC PSGYYGTRYP DINKCTKCKA
110 120 130 140 150
DCDTCFNKNF CTKCKSGFYL HLGKCLDNCP EGLEANNHTM ECVSIVHCEV
160 170 180 190 200
SEWNPWSPCT KKGKTCGFKR GTETRVREII QHPSAKGNLC PPTNETRKCT
210 220 230 240 250
VQRKKCQKGE RGKKGRERKR KKPNKGESKE AIPDSKSLES SKEIPEQREN
260 270
KQQQKKRKVQ DKQKSVSVST VH
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 41 | C → R in BAB55051 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 170 | R → I in BAB55051 (PubMed:14702039).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_018324 | 266 – 272 | VSVSTVH → GIEVTLAEGLTSVSQRTQPT PCRRRYL in isoform 2. 1 Publication | 7 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF251057 mRNA Translation: AAK34947.1 AK027346 mRNA Translation: BAB55051.1 AK314912 mRNA Translation: BAG37424.1 AL590733 Genomic DNA No translation available. AL031776 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48115.1 BC022367 mRNA Translation: AAH22367.1 |
CCDSi | CCDS5135.1 [Q9BXY4-1] |
RefSeqi | NP_116173.2, NM_032784.4 [Q9BXY4-1] |
Genome annotation databases
Ensembli | ENST00000356698.9; ENSP00000349131.4; ENSG00000146374.14 ENST00000368317.3; ENSP00000357300.3; ENSG00000146374.14 [Q9BXY4-2] |
GeneIDi | 84870 |
KEGGi | hsa:84870 |
MANE-Selecti | ENST00000356698.9; ENSP00000349131.4; NM_032784.5; NP_116173.2 |
UCSCi | uc003qar.5, human [Q9BXY4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF251057 mRNA Translation: AAK34947.1 AK027346 mRNA Translation: BAB55051.1 AK314912 mRNA Translation: BAG37424.1 AL590733 Genomic DNA No translation available. AL031776 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48115.1 BC022367 mRNA Translation: AAH22367.1 |
CCDSi | CCDS5135.1 [Q9BXY4-1] |
RefSeqi | NP_116173.2, NM_032784.4 [Q9BXY4-1] |
3D structure databases
AlphaFoldDBi | Q9BXY4 |
SMRi | Q9BXY4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 124315, 6 interactors |
CORUMi | Q9BXY4 |
IntActi | Q9BXY4, 5 interactors |
MINTi | Q9BXY4 |
STRINGi | 9606.ENSP00000349131 |
PTM databases
GlyGeni | Q9BXY4, 1 site |
iPTMneti | Q9BXY4 |
PhosphoSitePlusi | Q9BXY4 |
Genetic variation databases
BioMutai | RSPO3 |
DMDMi | 74752442 |
Proteomic databases
jPOSTi | Q9BXY4 |
MassIVEi | Q9BXY4 |
PaxDbi | Q9BXY4 |
PeptideAtlasi | Q9BXY4 |
PRIDEi | Q9BXY4 |
ProteomicsDBi | 79540 [Q9BXY4-1] 79541 [Q9BXY4-2] |
Protocols and materials databases
ABCDi | Q9BXY4, 1 sequenced antibody |
Antibodypediai | 32746, 292 antibodies from 33 providers |
DNASUi | 84870 |
Genome annotation databases
Ensembli | ENST00000356698.9; ENSP00000349131.4; ENSG00000146374.14 ENST00000368317.3; ENSP00000357300.3; ENSG00000146374.14 [Q9BXY4-2] |
GeneIDi | 84870 |
KEGGi | hsa:84870 |
MANE-Selecti | ENST00000356698.9; ENSP00000349131.4; NM_032784.5; NP_116173.2 |
UCSCi | uc003qar.5, human [Q9BXY4-1] |
Organism-specific databases
CTDi | 84870 |
DisGeNETi | 84870 |
GeneCardsi | RSPO3 |
HGNCi | HGNC:20866, RSPO3 |
HPAi | ENSG00000146374, Tissue enhanced (endometrium) |
MIMi | 610574, gene |
neXtProti | NX_Q9BXY4 |
OpenTargetsi | ENSG00000146374 |
PharmGKBi | PA134885289 |
VEuPathDBi | HostDB:ENSG00000146374 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3525, Eukaryota |
GeneTreei | ENSGT00940000157815 |
HOGENOMi | CLU_064219_0_0_1 |
InParanoidi | Q9BXY4 |
OMAi | WFFITLN |
OrthoDBi | 1441603at2759 |
PhylomeDBi | Q9BXY4 |
TreeFami | TF331799 |
Enzyme and pathway databases
PathwayCommonsi | Q9BXY4 |
Reactomei | R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-8939256, RUNX1 regulates transcription of genes involved in WNT signaling |
SignaLinki | Q9BXY4 |
SIGNORi | Q9BXY4 |
Miscellaneous databases
BioGRID-ORCSi | 84870, 9 hits in 1064 CRISPR screens |
ChiTaRSi | RSPO3, human |
GeneWikii | RSPO3 |
GenomeRNAii | 84870 |
Pharosi | Q9BXY4, Tbio |
PROi | PR:Q9BXY4 |
RNActi | Q9BXY4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000146374, Expressed in myometrium and 188 other tissues |
Genevisiblei | Q9BXY4, HS |
Family and domain databases
CDDi | cd00064, FU, 1 hit |
Gene3Di | 2.20.100.10, 1 hit |
InterProi | View protein in InterPro IPR006212, Furin_repeat IPR009030, Growth_fac_rcpt_cys_sf IPR042994, RSPO3 IPR043601, Rspo_Fu-CRD_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf IPR044004, TSP1_spondin_dom |
PANTHERi | PTHR46987:SF1, PTHR46987:SF1, 2 hits |
Pfami | View protein in Pfam PF15913, Furin-like_2, 1 hit PF19028, TSP1_spondin, 1 hit |
SMARTi | View protein in SMART SM00261, FU, 2 hits SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS50092, TSP1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RSPO3_HUMAN | |
Accessioni | Q9BXY4Primary (citable) accession number: Q9BXY4 Secondary accession number(s): B2RC27, Q5VTV4, Q96K87 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 16, 2006 |
Last sequence update: | June 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 158 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families